舒郁胶囊对孕前社会挫败应激大鼠子代学习记忆能力及CREB-BDNF信号通路的影响  

Effects of Shuyu capsules on learning and memory ability and CREB-BDNF signaling pathway of rats with pre-pregnancy social defeat stress

作　　者：刘坤 邢影 史经昊 李自发[2] 耿希文 魏盛[2] LIU Kun;XING Ying;SHI Jing-hao;LI Zi-fa;GENG Xi-wen;WEI Sheng(School of Traditional Chinese Medicine,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan 250355, China)

机构地区：[1]山东中医药大学中医学院,山东济南250355 [2]山东中医药大学实验中心,山东济南250355

出　　处：《中国药理学通报》2021年第10期1464-1468,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81974553,82004078);山东省自然科学基金资助项目(No ZR2019MH053,ZR2020ZD17);山东省高等学校“青创科技计划”立项支持团队(No 2019KJK002)。

摘　　要：目的探讨中药舒郁胶囊通过环腺苷酸反应元件结合蛋白-脑源性神经营养因子(CREB-BDNF)通路改善孕前社会挫败应激范式制备的肝疏泄不及大鼠模型雄性子代学习记忆能力的效应及作用机制。方法社会挫败应激制备的4组雌性大鼠(正常组、模型组、氟西汀组、舒郁胶囊组)经筛选后与雄性大鼠交配,其子代达2月龄后,每组各挑选12只雄性子代,对其进行物体识别实验及Morris水迷宫等行为学实验后取海马脑区,Western blot检测海马BDNF、CREB、pCREB表达。结果子代行为学指标结果显示,与正常组大鼠相比,模型组ORT 1 h及24 h识别指数下降、MWM探索期目标象限停留时间下降,逃避潜伏期上升;经氟西汀或舒郁胶囊干预可使上述指标得到改善。Western blot结果显示,与正常组大鼠相比,模型组海马BDNF、pCREB的含量及pCREB/CREB下降;氟西汀干预可明显纠正BDNF、pCREB及pCREB/CREB表达量,舒郁胶囊干预可明显纠正BDNF及pCREB/CREB表达量。结论中药舒郁胶囊可通过调节CREB-BDNF通路相关蛋白表达改善社会挫败应激制备的孕前肝疏泄不及大鼠模型雄性子代受损的学习记忆能力。Aim To investigate the effect of Shuyu capsules on the learning and memory ability of male offsprings of rat model prepared by pre-pregnancy social defeat stress by cyclic adenylate response element binding protein-brain-derived neurotrophic factor(CREB-BDNF)pathway and its mechanism.Methods Four groups of female rats(control group,model group,fluoxetine group and Shuyu capsule group)prepared by social defeat stress were screened and mate with male rats.When the offspring reached 2 months of age,12 male offsprings were selected from each group.The hippocampal region was extracted after object recognition test and Morris water maze behavior experiment.The expressions of BDNF,CREB and pCREB in hippocampus were detected by Western blot.Results The results of progeny behavior index showed that compared with control group,the ORT 1 h and 24 h recoginiton index,the target quadrant residence time in the MWM probe phase decreased in the model group and the escape latency in MWM probe phase increased.Fluoxetine and Shuyu capsules could improve the above indexes.Western blot results showed that compared with control group,the contents of BDNF,pCREB and pCREB/CREB in the hippocampus of model group decreased.Fluoxetine intervention could significantly correct the expression levels of BDNF,pCREB and pCREB/CREB,and Shuyu capsule intervention could significantly improve the expression levels of BDNF and pCREB/CREB.Conclusion Shuyu capsules can improve the impaired learning and memory ability of the male offsprings of the rat model of pre-pregnancy liver drainage induced by social defeat stress by regulating the expression of related proteins in CREB-BDNF pathway.

关 键 词：舒郁胶囊 CREB-BDNF通路 学习记忆 孕前社会挫败应激 雄性子代 抑郁症 

分 类 号：R-332[医药卫生] R282.71